99 articles - From Saturday Apr 23 2022 to Friday Apr 29 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
meta-analyses and systematic reviews
| Blood Cancer J |
Financial toxicity in hematological malignancies: a systematic review. The present systematic review identified that FT is common in patients with hematological malignancies and may be associated with poorer outcomes. However, studies of FT generally use non-standardized methods with cross-sectional analyses rather than longitudinal, prospective assessments. Further work is needed to standardize FT reporting and investigate measures to alleviate FT among patients with hematologic malignancies. |
| Lancet Haematol |
Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association. For ivosidenib, lestaurtinib, quizartinib, and venetoclax, we moderately recommend adjusting the dose of the antileukaemic agent during administration of triazoles. This is the first guidance supporting clinical decision making on antifungal prophylaxis in recipients of novel targeted drugs for acute myeloid leukaemia. Future studies including therapeutic drug monitoring will need to determine the role of dosage adjustment of novel antileukaemic drugs during concomitant administration of CYP3A4-inhibiting antifungals with respect to adverse effects and remission status. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Burden of disease, treatment utilization, and the impact on education and employment in patients with sickle cell disease: A comparative analysis of high- and low- to middle-income countries for the international Sickle Cell World Assessment Survey (SWAY). Although high overall satisfaction with current treatments was reported globally, most patients indicated a strong desire for alternative pain medications. There are likely several reasons for the relatively high patient-reported burden in the USA group compared with the HI/LMI countries, including an older population and differences in newborn screening programs and pediatric/adult transition of care. It is clear there is an urgent need for improved understanding and management of SCD globally, not just in the USA. |
EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk-stratification and management. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS. |
Hypercoagulability, endotheliopathy, and inflammation approximating 1 IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 |
Overexpression of the Energy Metabolism Transcriptome within Clonal Plasma Cells is Associated with the Pathogenesis and Outcomes of Patients with Multiple Myeloma. This was functionally confirmed by the clonal plasma cells from MM patients having a higher rate of mitochondrial and glycolysis-derived ATP formation than clonal plasma cells from MGUS patients. Thus, this study provides evidence for the effect of energy metabolism within clonal plasma cells on pathogenesis and outcomes of patients with MM. Exploiting the energy producing metabolic pathways within clonal plasma cells for diagnostic and therapeutic purposes in MM should be explored in the future. |
Proton pump inhibition for secondary hemochromatosis in hereditary anemia: a phase III placebo-controlled randomized cross-over clinical trial. NIH. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non-transfusion-dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators. |
TRAF3 alterations are frequent in del-3'IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3'IGH CLLs in terms of overall survival (NOTCH1, ATM and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3'IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients. |
| Ann Oncol |
Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial. The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favor of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT. |
| Blood |
Asciminib: new therapeutic option in chronic phase CML with treatment failure. Asciminib, a first-in-class allosteric inhibitor of BCR::ABL1 kinase activity, is now approved for the treatment of chronic phase CML patients who failed 2 lines of therapy or in patients with the T315I mutation. Promising attributes include high specificity and potency against BCR::ABL1, activity against most kinase domain mutations, and potential for combination therapy with ATP-competitive tyrosine kinase inhibitors (TKIs). Clinicians now have expanded third-line options which in most cases will involve a choice between asciminib and ponatinib. |
Combining daratumumab with CD47 blockade prolongs survival in preclinical models of pediatric T-ALL. However, T-ALL xenograft mice subjected to chemotherapy first (post-chemo MRD) and subsequently co-treated with Dara and Hu5F9-IgG2s displayed significantly reduced bone marrow infiltration as compared to single treatments. In relapsed and highly refractory T-ALL PDX combined treatment with Dara and Hu5F9-IgG2s was required to substantially prolong survival as compared to single treatments. These findings suggest that combining CD47 blockade with Dara is a promising therapy for T-ALL, especially for relapsed/refractory disease harbouring a dismal prognosis in patients. |
Inflammation and myeloid malignancy: Quenching the flame. Aberrant inflammatory activity impacts many different cells in the marrow, including normal blood and stromal marrow elements and leukemic cells, in unique and distinct ways. Inflammation can promote selective clonal expansion through differential immune-mediated suppression of normal hematopoietic cells and malignant clones. We review these complex roles, how they can be understood by separating cell-intrinsic from extrinsic effects, and how this informs future clinical trials. |
Intervening on the Storage Time of RBC Units and its Effects on Adverse Recipient Outcomes using Real-World Data. Treatment with RBC units exclusively fresher than 1-, 2-, 3-, and 4-weeks of storage was found to decrease the 28-day recipient mortality with 2.44 percentage points (pp) (0.86pp, 4.02pp), 1.93pp (0.85pp, 3.02pp), 1.06pp (-0.20pp, 2.33pp), and -0.26pp (-1.78pp, 1.25pp) as compared with transfusing exclusively older RBC units, respectively. The 28-day risk differences for the composite endpoint were similar. This study suggests that transfusing exclusively older RBC units stored for more than 1 or 2 weeks increases the 28-day recipient mortality and risk of thromboembolism or death compared with transfusing fresher RBC units. |
Mutant-SETBP1 activates transcription of Myc programs to accelerate CSF3R-driven myeloproliferative neoplasms. Through transcriptomic and epigenomic profiling, we found that SETBP1 enhances progenitor-associated programs-most strongly upregulating Myc and Myc target genes. This upregulation of Myc can be reversed by LSD1 inhibitors. In summary, we find that SETBP1 mutations promote aggressive hematopoietic cell expansion when expressed with mutant CSF3R through the upregulation of Myc-associated gene expression programs. |
Nf Transcriptome sequencing of single cells physically isolated after live dynamics quantification shows activation of different target gene programs in cells with different dynamics. Finally, artificial induction of oscillatory Nf |
Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI. This effectively targets the coagulation cascade to breaches of vascular integrity identified by patrolling platelets. Platelet-specific genetic loss of either CypD or TMEM16F as well as combined blockade of platelet GPIIBIIIA and GPVI reduce platelet PA in vivo and aggravate pulmonary inflammatory hemorrhage. Our findings illustrate a novel role of procoagulant platelets in the prevention of inflammatory bleeding and provide evidence that PA of patrolling platelet sentinels effectively targets and confines activation of coagulation to breaches of vascular integrity. |
Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease. In patients exposed to hydroxyurea, the aOR was 2.6 (95% CI: 1.1-6.4); it was 4.0 (95% CI: 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOE and should be limited in patients with SCD. |
Subclonal evolution of CLL driver mutations is associated with relapse in ibrutinib and acalabrutinib treated patients. As previously seen in patients treated with ibrutinib, the evolution of subclones containing CLL-driver mutations is significantly associated with negative outcomes for patients treated with acalabrutinib (Log-rank p=0.04). Subclones containing C481S BTK mutations (a well-known resistance mechanism) developed in three patients from each BTKi cohort in a median of 3 years (range=2-3.5). Understanding the clonal evolution within patients treated with either of these BTKis can help determine how well a patient maintains response to treatment and if BTKi treatment should be modified or another agent should be added to deepen response. |
Targeted autophagy disruption reveals the central role of macrophage iron metabolism in systemic iron homeostasis. Relatively high hepatic hepcidin expression, and decreased hepcidin level in the spleen of LysM-Atg5-/- mice correlating with low hemosiderin iron storage as well as in erythrophagocytic Atg5-/- macrophages were evidenced. Therefore, our results highligh the critical role of autophagy in macrophages for iron trafficking and systemic iron homeostasis. We propose that in macrophages, autophagy restricts ferroportin level and iron export resulting in hepcidin expression with an autocrine-paracrine effect that takes part in the regulation of the ferroportin expression in duodenal enterocytes. |
There and Back Again: The Once and Current Developments in Donor-Derived Platelet Products for Products for Hemostatic Therapy. Finally, whole blood offers the hemostatic spectrum of al blood components but has challenges, such as ABO incompatibility. While we know more than ever before about the in vitro properties of these products, clinical trial data on these products are accumulating. The purpose of this review is to summarize the findings of recent preclinical and clinical studies on alternative, donor-derived platelet products. |
Whole-genome sequencing reveals complex genomic features underlying anti-CD19 CAR T-cell treatment failures in lymphoma. In addition, the recurrent 3p21.31 chromosomal deletion containing the RHOA tumor suppressor was strongly enriched in patients failed by CAR-T therapy. Pretreatment reduced expression or mono-allelic loss of CD19 did not affect responses, suggesting CAR-19 therapy success and resistance are due to multiple mechanisms. Our study shows tumor-intrinsic genomic alterations are key among the complex interplay of factors that underly CAR-19 efficacy and resistance for large B-cell lymphomas. |
| Blood Adv |
A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease. A subset of DLI-derived Treg clones showed preferential expansion at week 8 and long-term persistence 1-year post-infusion. We demonstrate for the first time that infusion of polyclonal healthy donor Tregs followed by expansion with LD IL-2 is safe in patients with SR-cGVHD, thus establishing a foundation for future adoptive Treg therapies in the post-transplant setting. This trial is registered at as NCT01937468. |
ALLSorts: a RNA-Seq subtype classifier for B-Cell Acute Lymphoblastic Leukemia. Validation revealed that ALLSorts can accurately attribute samples to subtypes and can attribute multiple subtypes to a sample. Furthermore, when applied to both paediatric and adult cohorts, ALLSorts was able to classify previously undefined samples into subtypes. ALLSorts is available and documented on GitHub ( |
Burnout in U.S. hematologists and oncologists: impact of compensation models and advanced practice provider support. High advanced practice provider utilization was inversely associated with high burnout among community physicians. Distinct patterns of career dissatisfaction were observed between academic and community physicians. We propose that implementation of compensation models not based entirely on clinical productivity, increased support for women in academic medicine, and expansion of advanced practice provider support in community practices may address burnout among hematologists and oncologists. |
CD47 overexpression is common in intestinal non-GCB type diffuse large B-cell lymphoma and associated with 18q21 gain. CD47-high DLBCL was closely associated with 18q21 gain/amplification and showed a high prevalence in intestine. We propose to classify CD47-high DLBCL into intestinal and non-intestinal type. Further studies are necessary to assess whether the constellation of features seen here is reproducible and sufficient to consider primary intestinal DLBCL as a distinct biological entity. |
Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis. Dual inhibition of the MEK/ERK and PI3K/AKT pathways using a combination of trametinib and the PI3K inhibitor, taselisib, strongly suppressed B cell activation in vitro and improved mouse survival rate compared with vehicle or monotherapy with trametinib or taselisib. Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, while B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans. |
Evaluation of the combination therapy of hydroxyurea and thalidomide in ß-thalassemia. Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were non-responders; whereas, the responders had variable genetic mutations. A total of 38 adverse events were reported which resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with ß-thalassemia. |
Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder. Unexpectedly, the data demonstrate a functional interaction between the proteins encoded by the 2 alleles, with WT hTERT able to rescue the effect of K1050E on processivity, whereas L557P hTERT cannot. These data contribute to the mechanistic understanding of telomerase, indicating that RNA binding in 1 hTERT molecule affects the processivity of telomere addition by the other molecule. This work emphasizes the importance of functional characterization of TERT variants to reach a definitive molecular diagnosis for TBD patients, and in particular it illustrates the importance of analyzing the effects of compound heterozygous variants in combination to reveal interallelic effects. |
Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies. There were 3 partial and 2 complete responses, with overall response rate of 45% and median duration of response 6 months. Immediately following 10 days of IL-15, there was a median 7.2-fold increase in NK cells and 2.5-fold increase in circulating CD8+ T cells, while the number of circulating leukemic cells decreased by a median 38% across al dose levels. Treatment with IL-15 was associated with increased expression of NKp46 and NKG2D, markers of NK cell activation, as well as increased ex vivo ADCC activity of NK cells, while inhibitory receptors PD1 and Tim3 were decreased. |
Live imaging of platelets and neutrophils during antibody-mediated neurovascular thrombosis. Using real-time videomicroscopy to capture high velocity events in conjunction with unbiased computer assisted analyses, we provide images and quantifications of the cellular responses downstream Fc |
Loss of METTL3 Attenuates Blastic Plasmacytoid Dendritic Cell Neoplasm Response to PRMT5 Inhibition via IFN Signalling. Importantly, we discovered that this increase in interferon signalling attenuated the sensitivity of METTL3-depleted CAL-1 cells to PRMT5 inhibition. Correspondingly, stimulation of interferon signalling via TLR7 agonists weakened CAL-1 cells' sensitivity to PRMT5 inhibition. Overall, our findings implicate PRMT5 as a therapeutic target in BPDCN and provide insight into the involvement of METTL3 and interferon pathway in regulating response to PRMT5 inhibition. |
Npm1 Haploinsufficiency in collaboration with MEIS1 is sufficient to induce AML in mice. NPM1 haploinsufficiency alters MEIS1 binding occupancies such that it binds the promoter of the stem cell and cell cycle-associated oncogene, structural maintenance of chromosome protein 4 (SMC4) in NPM1 haploinsufficient AML cells but not in NPM1 wild type harboring Hoxa9/Meis1 transformed cells. SMC4 is higher expressed in haploinsufficient and NPM1c positive AML cells, which are more vulnerable to the disruption of the MEIS1-SMC4 axis compared to AML cells with non-mutated NPM1. Taken together, our study underlines that NPM1 haploinsufficiency on its own is a key factor of myeloid leukemogenesis and characterizes the MEIS1-SMC4 axis as a potential therapeutic target in this AML subtype. |
Outcomes for patients with severe chronic neutropenia treated with granulocyte colony-stimulating factor. Having cyclic or chronic autoimmune/idiopathic neutropenia portends a favorable prognosis. A few patients with idiopathic neutropenia evolve to develop lymphoid malignancies, but they do not appear to be at increased risk of myeloid malignancies, even with very long-term G-CSF therapy. Progression to systemic autoimmune diseases, bone marrow failure, aplastic anemia, or non-myeloid malignancies are not expected consequences of SCN or treatment with G-CSF. |
Phase 1 Study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma. All infused patients responded to CART-ddBCMA and 9/12 (75%) patients achieved CR/sCR. Responses deepened over time and at the time of last data-cut (median follow-up 56 weeks), 8/9 (89%) of evaluable patients achieved minimal residual disease negativity. In conclusion, the findings demonstrate the safety of CART-ddBCMA cells and document durable responses to CART-ddBCMA in RRMM patients. |
Phenotypic and genetic characterization of the Milan cohort of von Willebrand disease type 2. Among the 82 distinct variants identified, five different types including missense (n= 64), gene conversion (n= 10), synonymous (n= 1), deletion (n= 4) and splice (n= 3) were observed. The results of this large cohort showed that VWD type 2 is invariably due to variants that do not prevent the synthesis of the protein and the vast majority of patients (88%) had missense variants. Given the complexity of type 2 diagnosis and the necessity of performing several phenotypic tests, genetic analysis for patients suspected of type 2 is beneficial to establish the correct diagnosis. |
Platelet-targeted thrombolysis for treatment of acute ischemic stroke. SCE5-scuPA also improved neurological deficit, decreased intracerebral blood deposits, preserved the BBB and alleviated immunosuppression post-stroke. In MCAo, SCE5-scuPA did not worsen stroke outcomes or caused ICH, and protected the BBB. Our findings support the ongoing development of platelet-targeted thrombolysis with SCE5-scuPA as a novel emergency treatment for AIS with a promising safety profile. |
Platelets upregulate tumor programmed death-ligand 1 in an epidermal growth factor receptor-dependent manner in vitro. Instead, the high molecular weight epidermal growth factor (HWM-EGF) is abundant in platelets, which caused an upregulation of tumor cell PD-L1. Both an EGF neutralizing antibody and the drug, Cetuximab (EGF-receptor neutralizing antibody) inhibited platelet-induced increases in tumor cell PD-L1, suggesting that platelets induce tumor cell PD-L1 in an EGFR-dependent manner. Our data reveal a novel mechanism for platelets in tumor immune escape and warrant further investigation to determine if targeting platelets improves ICI therapeutic responses. |
Prediction of clinical outcome in CLL based on recurrent gene mutations, CLL-IPI variables, and (para)clinical data. Further emphasizing the high mortality due to infections in CLL, we found a close similarity between variables predictive of infection in the short outlook and those predictive of Death in the long outlook. We conclude that at the time of CLL diagnosis, routine (para)clinical data are more predictive of patient outcome than recurrent mutations. Future studies on modeling genetics and clinical outcome should always consider the inclusion of several (para)clinical data to improve performance. |
Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. The presence of a KMT2A rearrangement was the only pre-infusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI 9-17 months) and was particularly dismal in patients experiencing a LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplant, is critical and warrants further investigation on prospective clinical trials. |
Role of Stem Cell Transplant in CD30-positive PTCL following Frontline Brentuximab Vedotin+CHP or CHOP in ECHELON-2. The median PFS in patients who underwent SCT was not reached (95% CI, 49.81, NA), versus 55.66 months (95% CI, 19.88, NA) in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK-negative ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30-positive PTCL who achieve a CR following treatment with A+CHP. |
Storage of red blood cells in alkaline PAGGGM improves metabolism but has no effect on posttransfusion recovery. Our data indicate that despite better metabolic preservation, PAGGGM is not a suitable alternative for SAGM since storage in PAGGGM did not result in an increased PTR. Finally, RBCs that were recovered from circulation after transfusion showed reversal of the metabolic storage lesion in vivo within a day. This study is registered in the Dutch trial register (NTR6492). |
The Contribution of Rare Copy Number Variants in FAS Towards Pathogenesis of Autoimmune Lymphoproliferative Syndrome. The third subject had a paternally inherited ~0.044 Mb copy number loss encompassing exons 7-9 of FAS. Subjects with deletions in FAS had clinical presentations and biomarker profiles similar to ALPS subjects with germline and somatic FAS variants. We demonstrate that CNV analysis should be pursued if there is clinical and biomarker evidence of ALPS, as it can lead to a molecular diagnosis and appropriate treatment when FAS sequencing is inconclusive. |
Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse. Three objective responses were observed among 7 patients treated at the 2 higher DL, whereas no responses occurred at the 2 starting DL. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the Fc |
| Blood Cancer J |
Unsupervised machine learning improves risk stratification in newly diagnosed multiple myeloma: an analysis of the Spanish Myeloma Group. In conclusion, we describe a simple prognostic model for newly diagnosed MM whose predictions are independent of the ISS and R-ISS scores. Notably, the model is particularly useful in order to re-classify R-ISS score 2 patients in 2 different prognostic subgroups. The combination of ISS, R-ISS and unsupervised machine learning clusterization brings a promising approximation to improve MM risk stratification. |
| Haematologica |
Erdheim-Chester disease: look it in the eye. An orbital MRI study. Interestingly, ECD-ROD only rarely (7/45 (16%)) revealed the disease, with exophthalmos being the most frequently identified feature in this subgroup (3/45 (6%)). Even though ECD-ROD can be clinically silent, it constitutes a broad array of lesions often resulting in optic nerve signal abnormalities, the functional outcome of which remains to be established. ECD-ROD should thus be assessed initially and subsequently monitored by orbital MRI and ophthalmological follow-up. |
Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement. DNA methylation identified a cluster of V(D)J rearranged cases, clearly distinct from Burkitt leukaemia/lymphoma. Children with IG-MYC-r within that subgroup had 3-year EFS of 47% and OS of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this patient group must be allowed access to contemporary, minimal residual disease adapted, prospective clinical trial protocols. |
Phenotypic and functional characterization of the CD6-ALCAM T cell costimulatory pathway after allogeneic cell transplantation. Functional studies showed that itolizumab did not mediate direct cytolytic activity or antibody-dependent cytotoxicity in vitro. However, itolizumab efficiently abrogated the costimulatory activity of ALCAM on T cell proliferation, activation and maturation. Our results identify the CD6-ALCAM pathway as a potential target for aGVHD control and a phase I/II study using itolizumab as first line treatment in combination with steroids for patients with aGVHD is currently ongoing (NCT03763318). |
Resistance to PI3 The use of the IL-6R blocking antibody tocilizumab, the STAT3 inhibitor stattic, the LIN28 inhibitor LIN1632, the PDGFR inhibitor masitinib and the anti-CD19 antibody drug conjugate loncastuximab tesirine were active compounds in the resistant cells as single agents and/or in combination with PI3K//inhibition. Findings were validated on additional in vitro lymphoma models and on clinical specimens. A novel model of resistance obtained from splenic MZL allowed the identification of therapeutic approaches able to improve the anti-tumor activity of PI3Kttinhibitors in B-cell lymphoid tumors. |
The lymph node transcriptome of unicentric and idiopathic multicentric Castleman disease. Analysis of cytokine transcripts showed upregulation of CXCL13 but not IL-6 in UCD and iMCD. Among angiogenic mediators, the VEGFR1 ligand placental growth factor (PGF) was upregulated in both disease subtypes. We hereby report for the first time the whole lymph node transcriptome of UCD and iMCD, underscoring findings that could aid in the discovery of targetable disease mediators. |
Total late effect burden in long-term lymphoma survivors after highdose therapy with autologous stem-cell transplant and its effect on health-related quality of life. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high LE burden. The survivors had significantly poorer physical and mental HRQoL assessed by SF-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher LE burden (both p. |
| Lancet Haematol |
Venetoclax combined with induction chemotherapy in patients with newly diagnosed acute myeloid leukaemia: a post-hoc, propensity score-matched, cohort study. Venetoclax combined with intensive induction chemotherapy induced deep MRD-negative remissions, allowing transition to allogeneic HSCT in first remission, and improvement in event-free survival. These results highlight the incremental benefit of venetoclax added to intensive induction chemotherapy across European LeukemiaNet risk groups, and serve as a benchmark to inform enrolment on future confirmatory prospective clinical trials. None. |
| Leukemia |
CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study. Relapse occurred in 22 patients: 19/43 following 4-1BB-based CARs (12 CNS relapses), and 3/12 after CD28-based CARs with subsequent HSCT (no CNS relapse). Patients treated with tisagenlecleucel for an isolated CNS relapse had a high incidence of a subsequent CNS relapse (6 of 8). CAR T-cells were found to be effective in this cohort, though the risk of CNS relapse was not completely mitigated by this approach. |
Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia. Addition of sulfasalazine at a clinically relevant concentration significantly augmented the anti-leukemic activity of a daunorubicin-cytarabine combination in a panel of 45 primary samples enriched in NPM1-mutated AML. These results were confirmed in vivo in a patient-derived xenograft model. Collectively, our results nominate cystine import as a druggable target in AML and raise the possibility to repurpose sulfasalazine for the treatment of AML, notably in combination with chemotherapy. |
Development of [211At]astatine-based anti-CD123 radioimmunotherapy for acute leukemias and other CD123+ malignancies. CD123+ cell targeting studies in immunodeficient mice demonstrated specific uptake of 211 At-labeled anti-CD123 mAbs in human CD123+ MOLM-13 cell tumors in the flank. In mice injected intravenously with MOLM-13 cells or a CD123 NULL MOLM-13 subline, a single dose of up to 40 |
Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15. g., CD48, CD74, and CD86) in DR(-) cells, which was not evident in HLA-class I(-) HSPCs. DR(-) cells were exclusively detected in GPI(+) HSPCs in four patients whose HSPCs could be analyzed separately for GPI(+) and GPI(-) HSPCs. These findings suggest that CD4 + T cells specific to antigens presented by HLA-DR15 on HSPCs may contribute to the development of AA as well as the immune escape of GPI(-) HSPCs in a distinct way from CD8 + T cells recognizing HLA-class I-restricted antigens. |
Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT. |
Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma. 4/7 patients with TP53 variants responded. Deletion of the histone methyltransferase SETD2 sensitised to HMA but TET2 deletion did not. Guadecitabine conveyed an acceptable ORR and toxicity profile; decitabine analogues may provide a backbone for future combinatorial regimens co-targeting histone methyltransferases. |
Leukotrienes promote stem cell self-renewal and chemoresistance in acute myeloid leukemia. In vitro, and in vivo genetic, and pharmacologic perturbation studies confirm that ALOX5 positively regulates the leukemogenic potential of AML LSCs, and its loss does not significantly affect the function of normal HSPCs. ALOX5 mediates resistance to daunorubicin (DNR) and promotes AML cell survival and maintenance through its leukotriene (LT) synthetic capacity, specifically via modulating the synthesis of LTB4 and its binding to LTB receptor (BLTR). Our study reveals a previously unrecognized role of LTs in AML pathogenesis and chemoresistance, whereby inhibition of ALOX5 mediated LTB4 synthesis and function could be combined with standard chemotherapy, to enhance the overall therapeutic efficacy in AML. |
| Thromb Haemost |
Inhibition of HIF prolyl hydroxylase modulates platelet function. Further, IOX-2 significantly upregulated HIF-1 |
Perioperative coagulation profile in major liver resection for cancer: a prospective observational study. The ratio of the anticoagulant protein C to the procoagulant FVIII was low at baseline and further declined postoperatively, indicating a prothrombotic state. Though no bleeding complications were reported, one patient experienced pulmonary embolism while under thromboprophylaxis. Overall, patients with hepatic carcinoma presenting for elective major hepatectomy may have baseline malignancy associated coagulation disturbances, aggravating the hypercoagulable state documented in the early postoperative period. |
PREGNANCY AFTER COMBINED ORAL CONTRACEPTIVE-ASSOCIATED VENOUS THROMBOEMBOLISM: AN INTERNATIONAL RETROSPECTIVE STUDY OF OUTCOMES. Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique LMWH-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
| Blood |
Clinical features of thrombosis and bleeding in COVID-19. Laboratory parameters associated with higher thrombotic risk include higher D-dimer, low fibrinogen and low lymphocyte count, with higher FVIII and von Willebrand factor levels indicative of more severe COVID-19 infection. All patients should receive thromboprophylaxis when admitted with COVID-19 infection, but the dose and length of treatment still remain debated. Treatment for thrombosis remains as per standard VTE guidelines, but adjustments may be required depending on other factors relevant to the patient admission. |
| Blood Cancer J |
| CA Cancer J Clin |
Clinical management of metastatic colorectal cancer in the era of precision medicine. This approach could result in the identification of individual prognostic and predictive parameters, which could help the clinician in choosing the most appropriate therapeutic program(s) throughout the entire disease journey for each patient with mCRC. CA Cancer J Clin. 2022;72:000-000. |
| J Hematol Oncol |
Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies. |
| Lancet Haematol |
Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report. |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Adv |
| Blood Cancer J |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |